BACKGROUND:Studies have shown that platelet-derived growth factor BB can stimulate the proliferation and osteogenic differentiation of mesenchymal stem cells and accelerate the calcification process of osteoblast-like cells.However,its clinical application has problems such as short half-life and easy decomposition.Loading the growth factor onto a suitable biomaterial scaffold can enable its slow and continuous release and maintain an effective concentration,which has become a hot topic in current research.OBJECTIVE:To observe the effect of chitosan/reduced graphene oxide scaffolds loaded with platelet-derived growth factor BB on the repair of alveolar bone defect in rats.METHODS:(1)Chitosan/reduced graphene oxide scaffolds(referred to as CS/rGO scaffolds)and chitosan/reduced graphene oxide scaffolds loaded with different mass concentrations(5,10,15,and 20 mg/L)of platelet-derived growth factor BB(referred to as CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds)were prepared respectively.The five groups of scaffolds were co-cultured with rat periodontal ligament stem cells.The cell proliferation and migration were detected by CCK-8 assay and Transwell chamber assay,respectively,to screen the appropriate growth factor loading mass concentration for subsequent experiments.CS/rGO scaffolds(or extracts)and CS/rGO/PDGF-BB-15 scaffolds(or extracts)were co-cultured with rat periodontal ligament stem cells,and the osteogenic differentiation and angiogenic ability of the cells were detected.(2)The alveolar bone defect model was prepared in front of the bilateral maxillary first molars of 16 SD rats,and the rats were randomly divided into 4 intervention groups:the blank control group did not receive any intervention,the simple scaffold group was implanted with CS/rGO/PDGF-BB-15 scaffold,the control group was implanted with CS/rGO scaffold and rat periodontal ligament stem cell complex,and the experimental group was implanted with CS/rGO/PDGF-BB-15 scaffold and rat periodontal ligament stem cell complex,with 4 rats in each group.Twelve weeks after surgery,the bone repair of the alveolar bone defect was observed by Micro CT scanning and hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds could promote the proliferation and migration of rat periodontal ligament stem cells.Among them,the CS/rGO/PDGF-BB-15 scaffold had the most significant effect on promoting cell proliferation and migration,and this scaffold was used for subsequent experiments.Compared with the CS/rGO scaffold,the CS/rGO/PDGF-BB-15 scaffold could promote the osteogenic and angiogenic differentiation of rat periodontal ligament stem cells.(2)Micro CT scanning and hematoxylin-eosin staining results showed that the experimental group had the best alveolar bone defect repair effect,and a large amount of new bone tissue and blood vessel formation could be seen.(3)The chitosan/reduced graphene oxide scaffold loaded with platelet-derived growth factor BB can effectively promote the repair of rat alveolar bone defects by promoting the proliferation,migration,angiogenic and osteogenic differentiation of rat periodontal ligament stem cells.

BACKGROUND:Studies have shown that platelet-derived growth factor BB can stimulate the proliferation and osteogenic differentiation of mesenchymal stem cells and accelerate the calcification process of osteoblast-like cells.However,its clinical application has problems such as short half-life and easy decomposition.Loading the growth factor onto a suitable biomaterial scaffold can enable its slow and continuous release and maintain an effective concentration,which has become a hot topic in current research.OBJECTIVE:To observe the effect of chitosan/reduced graphene oxide scaffolds loaded with platelet-derived growth factor BB on the repair of alveolar bone defect in rats.METHODS:(1)Chitosan/reduced graphene oxide scaffolds(referred to as CS/rGO scaffolds)and chitosan/reduced graphene oxide scaffolds loaded with different mass concentrations(5,10,15,and 20 mg/L)of platelet-derived growth factor BB(referred to as CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds)were prepared respectively.The five groups of scaffolds were co-cultured with rat periodontal ligament stem cells.The cell proliferation and migration were detected by CCK-8 assay and Transwell chamber assay,respectively,to screen the appropriate growth factor loading mass concentration for subsequent experiments.CS/rGO scaffolds(or extracts)and CS/rGO/PDGF-BB-15 scaffolds(or extracts)were co-cultured with rat periodontal ligament stem cells,and the osteogenic differentiation and angiogenic ability of the cells were detected.(2)The alveolar bone defect model was prepared in front of the bilateral maxillary first molars of 16 SD rats,and the rats were randomly divided into 4 intervention groups:the blank control group did not receive any intervention,the simple scaffold group was implanted with CS/rGO/PDGF-BB-15 scaffold,the control group was implanted with CS/rGO scaffold and rat periodontal ligament stem cell complex,and the experimental group was implanted with CS/rGO/PDGF-BB-15 scaffold and rat periodontal ligament stem cell complex,with 4 rats in each group.Twelve weeks after surgery,the bone repair of the alveolar bone defect was observed by Micro CT scanning and hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds could promote the proliferation and migration of rat periodontal ligament stem cells.Among them,the CS/rGO/PDGF-BB-15 scaffold had the most significant effect on promoting cell proliferation and migration,and this scaffold was used for subsequent experiments.Compared with the CS/rGO scaffold,the CS/rGO/PDGF-BB-15 scaffold could promote the osteogenic and angiogenic differentiation of rat periodontal ligament stem cells.(2)Micro CT scanning and hematoxylin-eosin staining results showed that the experimental group had the best alveolar bone defect repair effect,and a large amount of new bone tissue and blood vessel formation could be seen.(3)The chitosan/reduced graphene oxide scaffold loaded with platelet-derived growth factor BB can effectively promote the repair of rat alveolar bone defects by promoting the proliferation,migration,angiogenic and osteogenic differentiation of rat periodontal ligament stem cells.

ObjectiveTo evaluate the clinical efficacy and safety of acupuncture in treating severe Bell's palsy and to explore its potential mechanism by investigating the effect on serum levels of glial cell line-derived neurotrophic factor （GDNF） and nerve growth factor （NGF）. MethodsA randomized， subject-blinded， sham-acupuncture controlled trial was conducted. A total of 130 patients with severe Bell's palsy were randomly allocated into a treatment group or a control group at a 1∶1 ratio. Both groups received conventional western medicine. In addition， the treatment group received acupuncture， while the control group received sham acupuncture， with each session lasting 30 minutes. The treatment course lasted 8 weeks for both groups， followed by a follow-up assessment at week 12. The primary outcome was the proportion of patients achieving House-Brackmann （H-B） grade Ⅱ or lower at week 8. Secondary outcomes included Sunnybrook facial grading system scores at week 0， 4， 8， and 12， the time to satisfactory recovery（the time required to achieve H-B grade≤Ⅱ）， distribution of H-B grades and facial disability index （FDI） scores including the physical function subscale （FDIP） and social/well-being function subscale （FDIS） scores at week 0， 4， 8， and 12， and serum GDNF and NGF levels at week 0， 4， and 8. Adverse events and participants' self-assessments of treatment efficacy were also recorded. ResultsA total of 122 participants completed the study， including 62 in the treatment group and 60 in the control group. An intention-to-treat （ITT） analysis was performed， and missing data were handled using the last observation carried forward （LOCF） method. The proportion of patients achieving H-B grade ≤grade Ⅱ at week 8 was 78.5% （51/65） in the treatment group， significantly higher than 49.2% （32/65） in the control group （P＜0.05）. The Sunnybrook scores， FDIP and FDIS scores increased， while H-B grades decreased at week 4， 8， and 12 in both groups compared to week 0； moreover， improvements in all outcome measures were significantly greater in the treatment group than in the control group （P＜0.05）. The median time to satisfactory recovery was 6 weeks （95%CI： 5.697-6.303） in the treatment group， significantly shorter than 12 weeks （95%CI： 8.314-15.686） in the control group （P＜0.05）. Serum levels of GDNF and NGF were significantly higher in the treatment group at weeks 4 and 8 （P＜0.05）. No serious acupuncture-related adverse events occurred in either group. Adverse events were reported in 5 patients （7.69%） in the treatment group and 4 patients （6.15%） in the control group， with no statistically significant difference between groups （P＞0.05）. Patients' self-assessment of treatment efficacy after 8 weeks treatment was significantly better in the treatment group （P＜0.05）. ConclusionAcupuncture can effectively improve facial nerve function and shorten recovery time in patients with severe Bell's palsy， with a favorable safety profile. The therapeutic mechanism may be associated with the upregulation of serum GDNF and NGF levels.

Nitrofurazone(NFZ)is an antibiotic that is used as a veterinary drug in aquaculture.NFZ abuse can lead to a series of environmental and health issues,making it crucial to establish a rapid and highly sensitive method for NFZ detection.In this study,platinum nanoparticle(PtNPs)-loaded zeolitic imidazolate framework(ZIF-8)was used as a precursor,and PtNPs functionalized nitrogen doped porous carbon(NC)was obtained through pyrolysis.Pt@NC was combined with multi-walled carbon nanotubes(MWCNTs)and cast onto a glassy carbon electrode(GCE)surface to construct an electroch-emical sensor.Electrochemical tests revealed that Pt@NC/WCNT/GCE exhibited an electrochemical active area of 0.066 cm2 and a heterogeneous electron transfer rate constant(k0)of 2.03×10-3 cm/s,which were higher than other materials.Compared with the electrodes modified by other materials,the NFZ generated the highest peak current of irreversible reduction peak on the Pt@NC/WCNT/GCE electrode.In comparison with Pt@ZIF-8/WCNT/GCE,after pyrolysis and carbonization treatment,the reduction current of NFZ increased by 2.19 times,and the reduction peak potential shifted positively by 19 mV simultaneously.When compared with NC/WCNT/GCE,the PtNPs in the composite material enhanced the NFZ current by 4.25 times.Additionally,the experimental conditions for detecting NFZ using the sensor were optimized,including the carbonization temperature of Pt@ZIF-8,ratio of Pt@NC to CNT,loading amount of the modified material,and electrolyte pH.Under the optimized conditions,the sensor demonstrated a linear detection range for NFZ of 0.20-240 μmol/L,a sensitivity of 9.995 μA/((μmol/L)?cm2)and a limit of detection(LOD)of 0.06 μmol/L.The sensor exhibited excellent anti-interference capability,good reproducibility,and stability,with spiked recoveries for NFZ in water samples ranging from 94.6%to 105.6%.This study provided a novel electrochemical sensing approach for NFZ detection.

Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia（MPP）in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized，controlled，multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1，2023 to January 31，2024 were included.According to the severity of pneumonia，they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP（SMPP/RMPP）group with 160 cases，and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1，using the random number table method.After screening，subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin，while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT，length of hospital stay，duration of fever，cough score，whether mild cases developed into severe or refractory cases，duration of hormone use，use of intravenous immunoglobulin（IVIG），bronchoscopy treatment，and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication，vital signs，blood routine，urine routine，liver function，myocardial enzymes，renal function，and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals，including 118 cases in the experimental group and 113 cases in the control group.Main observation index：the rate of lung CT aggravation in the experimental group was lower than that in the control group（2.6% vs 15.3%， P<0.01），and the difference was statistically significant.Secondary indexes：there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.However，the rate of cases of plastic bronchitis（PB）found under bronchoscopy in the experimental group was lower than that in the control group（0 vs 18.8%， P=0.03），and the difference was statistically significant.Among the mild MPP（72 cases），there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and the improvement rate of lung CT between the two groups（all P>0.05）.However，compared with the control group，the rate of cases developing into SMPP/RMPP in the experimental group was less（24.3% vs 48.6%， P=0.03），and the difference in IgG before and after treatment was small［0.53（-0.04，1.18）g/L vs 1.33（0.48，2.25）g/L， P=0.01］.Among the SMPP/RMPP cases（159 cases），the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group（0 vs 20%， P=0.04），and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group（1.3% vs 19.5%， P<0.01），and the improvement rate of lung CT in the experimental group was higher than that in the control group（88.8% vs 75.3%， P=0.03），with statistically significant differences.There were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.Two cases in the experimental group developed rashes，which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine，liver function，myocardial enzymes，renal function，electrocardiogram，and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP，reduce the rate of aggravation of the image findings，promote the absorption of lung inflammation，reduce the rate of PB found under bronchoscopy，and has good safety.

Objective:To evaluate the perioperative application effect of enhanced recovery after surgery (ERAS) clinical pathway in percutaneous vertebro plasty (PVP).Methods:The clinical data of 274 patients who underwent PVP treatment for osteoporotic vertebral compression fracture (OVCF) in Beijing Friendship Hospital, Capital Medical University from May 2023 to August 2024 were retrospectively analyzed. The patients were divided into two groups according to the different numbers of surgical segments: the single-segment group ( n=211) and the multisegment group ( n=63). Patients in the single-segment group underwent single-segment surgery, while patients in the multisegment group underwent surgery on ≥2 segments. The core points of the ERAS clinical pathway adopted in this study include perioperative education, pain management, early mobilization, application of "outfast", and joint guidance from the departments of nutrition and rehabilitation. Comparison was made between the two groups of patients in terms of visual analog scale (VAS) scores for low back pain at preoperative, 2 h, 6 h, 24 h postoperatively, and on the day of discharge; Oswestry disability index (ODI) scores preoperatively and on the day of discharge; time to first ambulation postoperatively, total length of hospital stay, postoperative length of stay, perioperative complications, and perioperative application of Opioid consumption. Measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; count data were expressed as cases and percentage, and the Chi-square test was used for comparison between groups. The VAS pain scores at each stage of the perioperative period were evaluated using repeated measures analysis of variance or generalized estimating equations. Results:Compared with that before the operation [(6.17±0.93) points, (6.29±0.83) points], the VAS scores of low back pain of patients in the single-segment group and the multisegment group at 2 hours after surgery [(3.09±0.82) points, (3.27±0.65) points], 6 hours after surgery [(2.60±0.79) points, (2.62±0.55) points], and 24 hours after surgery [(1.89±0.77) points, (1.97±0.72) points] and on the day of discharge [(1.72±0.71) points, (1.81±0.64) points] were significantly decreased, and the differences were statistically significant ( P<0.05). At the same stage, the VAS scores of low back pain in both groups were not statistically significant ( P>0.05). The ODI scores of patients in the single-segment group and the multisegment group on the day of discharge [(24.21±2.35) points, (24.63±3.31) points] were significantly lower than those before the operation [(64.50±4.81) points, (65.52±4.08) points], and the differences were statistically significant ( P<0.05). There were no statistically significant differences in perioperative complications and the proportion of Opioid drug application between the two groups of patients ( P>0.05). Conclusion:For patients with single-segment or multisegment OVCF, PVP surgical treatment under ERAS clinical pathway management can achieve immediate pain relief, early ambulation exercise, and satisfactory perioperative efficacy.

Objective:To evaluate preoperative malnutrition risk in patients with osteoporotic vertebral compression fracture (OVCF) based on mini nutritional assessment short form (MNA-SF) and analyze the related clinical risk factors.Methods:A cross-sectional study was conducted using clinical data from 129 OVCF patients who underwent percutaneous vertebroplasty at Beijing Friendship Hospital, Capital Medical University, between May 2023 and December 2023. The cohort included 26 males and 103 females, aged (74.71±9.13) years(ranging from 48-98 years). According to MNA-SF scoring method, they were divided into three groups, the malnutrition group ( n=6), the nutritional risk group ( n=40), and the good nutrition group ( n=83). Nutritional risk and malnutrition rates were evaluated using the MNA-SF score. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s) and compared using one-way ANOVA. The comparison between groups of count data was conducted using chi-square test. Univariate analysis and multivariate logistic regression were performed to identify independent risk factors for malnutrition and nutritional risk. Results:According to the MNA-SF score, among 129 patients, the malnutrition rate was 4.7%, the nutritional risk rate was 31.0%, and 64.3% exhibited adequate nutrition based on MNA-SF scores. The results of one-way ANOVA showed that gender ( P=0.023) and BMI ( P<0.001) were significantly correlated with malnutrition and nutritional risk; Logistic regression analysis suggested that the influencing factors of nutritional risk included gender ( P=0.002) and BMI ( P<0.001), while the only dangerous factor of malnutrition was BMI ( P<0.001). Conclusions:Bsed on MNA-SF, OVCF patients undergoing percutaneous vertebroplasty have a higher incidence of malnutrition and nutritional risk. The risk factors for nutritional risk in patients are gender and BMI, while the risk factor for malnutrition is only BMI.

This study aims to explore the mechanism of Buyang Huanwu Decoction(BHD) in promoting angiogenesis after oxygen-glucose deprivation/reoxygenation(OGD/R) of mouse brain microvascular endothelial cell line(brain-derived Endothelial cells.3, bEnd.3) based on the caveolin-1(Cav1)/Yes-associated protein 1(YAP1)/hypoxia-inducible factor-1α(HIF-1α) signaling pathway. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze the blood components of BHD. The cell counting kit-8(CCK-8) method was used to detect the optimal intervention concentration of drug-containing serum of BHD after OGD/R injury of bEnd.3. The lentiviral transfection method was used to construct a Cav1 silent stable strain, and Western blot and polymerase chain reaction(PCR) methods were used to verify the silencing efficiency. The control bEnd.3 cells were divided into a normal group(sh-NC control group), an OGD/R model + blank serum group(sh-NC OGD/R group), and an OGD/R model + drug-containing serum group(sh-NC BHD group). Cav1 silent cells were divided into an OGD/R model + blank serum group(sh-Cav1 OGD/R group) and an OGD/R model + drug-containing serum group(sh-Cav1 BHD group). The cell survival rate was detected by the CCK-8 method. The cell migration ability was detected by a cell migration assay. The lumen formation ability was detected by an angiogenesis assay. The apoptosis rate was detected by flow cytometry, and the expression of YAP1/HIF-1α signaling pathway-related proteins in each group was detected by Western blot. Finally, co-immunoprecipitation was used to verify the interaction between YAP1 and HIF-1α. The results showed astragaloside Ⅳ, formononetin, ferulic acid, and albiflorin in BHD can all enter the blood. The drug-containing serum of BHD at a mass fraction of 10% may be the optimal intervention concentration for OGD/R-induced injury of bEnd.3 cells. Compared with the sh-NC control group, the sh-NC OGD/R group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, significantly increased cell apoptotic rate, significantly lowered phosphorylation level of YAP1 at S127 site, and significantly elevated nuclear displacement level of YAP1 and protein expression of HIF-1α, vascular endothelial growth factor(VEGF), and vascular endothelial growth factor receptor 2(VEGFR2). Compared with the same type of OGD/R group, the sh-NC BHD group and sh-Cav1 BHD group had significantly increased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly decreased cell apoptotic rate, a further decreased phosphorylation level of YAP1 at S127 site, and significantly increased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC OGD/R group, the sh-Cav1 OGD/R group exhibited significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC BHD group, the sh-Cav1 BHD group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at the S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. YAP1 protein was present in the protein complex precipitated by the HIF-1α antibody, and HIF-1α protein was also present in the protein complex precipitated by the YAP1 antibody. The results confirmed that the drug-containing serum of BHD can increase the activity of YAP1/HIF-1α pathway in bEnd.3 cells damaged by OGD/R through Cav1 and promote angiogenesis in vitro.
Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Signal Transduction/drug effects* ; Glucose/metabolism* ; Caveolin 1/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; YAP-Signaling Proteins ; Oxygen/metabolism* ; Endothelial Cells/metabolism* ; Cell Line ; Adaptor Proteins, Signal Transducing/genetics* ; Neovascularization, Physiologic/drug effects* ; Cell Hypoxia/drug effects* ; Angiogenesis

Thrombospondin 4 (THBS4; TSP4), a crucial component of the extracellular matrix (ECM), serves as an important regulator of tissue homeostasis and various pathophysiological processes. As a member of the evolutionarily conserved thrombospondin family, THBS4 is a multidomain adhesive glycoprotein characterized by six distinct structural domains that mediate its diverse biological functions. Through dynamic interactions with various ECM components, THBS4 plays pivotal roles in cell adhesion, proliferation, inflammation regulation, and tissue remodeling, establishing it as a key modulator of microenvironmental organization. The transcription and translation of THBS4 gene, as well as the activity of the THBS4 protein, are tightly regulated by multiple signaling pathways and extracellular cues. Positive regulators of THBS4 include transforming growth factor-β (TGF-β), interferon-γ (IFNγ), granulocyte-macrophage colony-stimulating factor (GM-CSF), bone morphogenetic proteins (BMP12/13), and other regulatory factors (such as B4GALNT1, ITGA2/ITGB1, PDGFRβ, etc.), which upregulate THBS4 at the mRNA and/or protein level. Conversely, oxidized low-density lipoprotein (OXLDL) acts as a potent negative regulator of THBS4. This intricate regulatory network ensures precise spatial and temporal control of THBS4 expression in response to diverse physiological and pathological stimuli. Functionally, THBS4 acts as a critical signaling hub, influencing multiple downstream pathways essential for cellular behavior and tissue homeostasis. The best-characterized pathways include: (1) the PI3K/AKT/mTOR axis, which THBS4 modulates through both direct and indirect interactions with integrins and growth factor receptors; (2) Wnt/β-catenin signaling, where THBS4 functions as either an activator or inhibitor depending on the cellular context; (3) the suppression of DBET/TRIM69, contributing to its diverse regulatory roles. These signaling connections position THBS4 as a master regulator of cellular responses to microenvironmental changes. Substantial evidence links aberrant THBS4 expression to a range of pathological conditions, including neoplastic diseases, cardiovascular disorders, fibrotic conditions, neurodegenerative diseases, musculoskeletal disorders, and atopic dermatitis. In cancer biology, THBS4 exhibits context-dependent roles, functioning either as a tumor suppressor or promoter depending on the tumor type and microenvironment. In the cardiovascular system, THBS4 contributes to both adaptive remodeling and maladaptive fibrotic responses. Its involvement in fibrotic diseases arises from its ability to regulate ECM deposition and turnover. The diagnostic and therapeutic potential of THBS4 is particularly promising in oncology and cardiovascular medicine. As a biomarker, THBS4 expression patterns correlate significantly with disease progression and patient outcomes. Therapeutically, targeting THBS4-mediated pathways offers novel opportunities for precision medicine approaches, including anti-fibrotic therapies, modulation of the tumor microenvironment, and enhancement of tissue repair. This comprehensive review systematically explores three key aspects of THBS4 research(1) the fundamental biological functions of THBS4 in ECM organization; (2) its mechanistic involvement in various disease pathologies; (3) its emerging potential as both a diagnostic biomarker and therapeutic target. By integrating recent insights from molecular studies, animal models, and clinical investigations, this review provides a framework for understanding the multifaceted roles of THBS4 in health and disease. The synthesis of current knowledge highlights critical research gaps and future directions for exploring THBS4-targeted interventions across multiple disease contexts. Given its unique position at the intersection of ECM biology and cellular signaling, THBS4 represents a promising frontier for the development of novel diagnostic tools and therapeutic strategies in precision medicine.

Objective:To investigate the preventive and therapeutic effects and mechanisms of Dachaihu decoction(DCD)on dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)and liver injury in mice,as well as the association between DCD benefits and gut microbiota modulation.Methods:Mice were treated with DCD(20.10 and 10.05 g/kg)for 2 weeks,with free access to drinking water containing 3%DSS in the second week to induce UC.Histopathological examination,RT-qPCR and 16S rRNA sequencing were used to investigate the effect of DCD on UC mice.Results:DCD pretreatment significantly alleviated weight loss,bloody diarrhea with mucus,histopathological abnormalities of the colon,and colon shortening in mice with DSS-induced UC.In addition,DCD pretreat-ment significantly upregulated the levels of Occludin,ZO-1,and MUC-2 in the colon and protected the intestinal barrier of mice.DCD pretreatment also alleviated inflammatory cell infiltration in the colon and the liver and significantly reduced the expression levels of the proinflammatory factors such as IL-1β,IL-6,TNF-α,iNOS,COX-2,and NLRP3,thereby exerting a protective effect against UC and liver injury.It should be noted that DCD corrected gut micro-biota imbalance in UC mice by enriching probiotic bacteria such as Lactobacillus and Bifidobacterium and reducing harmful bacteria such as Norank_f_Desulfovibrionaceae and Escherichia-Shigella.Conclusion:DCD can alleviate DSS-induced UC and exert a liver-protecting effect by protecting intestinal barrier,inhibiting inflam-mation,and regulating gut microbiota.